Instrumentation for performing time-of-flight (TOF) mass spectral analysis to determine the mass of an ionized molecule has been known for several decades. By measuring the velocity (v) of an ion having a known kinetic energy (KE), its mass (m) can be determined via the well known relationship: ##EQU1##
A typical two-step linear time-of-flight mass spectrometer 10 (TOFMS) shown in FIG. 1 has three distinct regions. For gas phase sample sources, the gas circulates within region 1 of width d.sub.1 located between grids (or plates) G.sub.0 12 and G.sub.1 16. Within region 1, ions 24 and 26 are produced from the sample using, for example, an electron beam or a laser. Ions 24 and 26 are ideally formed at a position X.sub.0 and then accelerated to the same kinetic energy by electric fields E.sub.1, generated within region 1, and E.sub.2, generated within region 2, where region 2 is of width d.sub.2 and is located between grids (or plates) G.sub.1 16 and G.sub.2 18. Electric field E.sub.1 is achieved in the direction shown in FIG. 1 to accelerate positively charged ions by applying appropriate voltage potentials to the grids (or plates) G.sub.0 12 and G.sub.1 16. Similarly, electric field E.sub.2 is achieved in the direction shown to accelerate positively charged ions by applying appropriate voltage potentials to the grids (or plates) G.sub.1 16 and G.sub.2 18. It should be noted that electric fields E.sub.1 and E.sub.2 may be reversed in direction, by applying voltage potentials of appropriate magnitudes to grids (or plates) G.sub.0 12, G.sub.1 16 and G.sub.2 18, to accelerate negatively charged ions to the same kinetic energy in the direction shown in FIG. 1.
Within the field free drift region 20 of length L, ions with different mass to charge ratios separate in space and time. For example, if ion 24 has mass m.sub.1 and ion 26 has mass m.sub.2, where m.sub.2 is greater than m.sub.1, then ion 24 will reach the end 22 of the drift region 20 before ion 26. A detector 28 is typically located at the end 22 of the drift region 20 for recording the arrival of ions as a function of time. Thus, the difference between the start time, common to all ions generated within region 1, and the arrival time, at the detector 28, of a packet of ions having the same mass is a function of their mass to charge ratio (m/z), and can therefore be used to calculate the mass of the ions.
If an ion's flight time was strictly dependent upon its mass-to-charge ratio, the TOFMS 10 (or any other TOFMS instrument) would have unlimited resolution. In practice, however, an ion's time-of-flight additionally depends upon space charge effects, inhomogeneous electric fields, the finite frequency response of the detector 28 and associated signal processing electronics, the temporal spread of the ionization source, the initial distribution of ion velocities and the spatial spread of ions within the source region (region 1). These additional dependencies combine to decrease resolution in the TOFMS 10 by increasing the measured time width of the ion packet that reaches the detector 28.
Space charge effects are manifest in an increased velocity spread due to coulombic repulsions or attractions between ions and can be reduced by using low power lasers or sample pressures. Careful design and construction of the acceleration grids G.sub.0 -G.sub.2 reduces the effects of fringing fields, grid deformation and electric field punching through the grids. Using high-frequency pulse counting techniques can extend the resolution of the detection/signal processing electronics into the picosecond regime and state-of-the-art picosecond laser sources can virtually eliminate the temporal spread of the laser ionization source as a significant factor in ion peak width. Thus, under normal operating conditions, resolution in the TOFMS 10 is dominated by the initial velocity and spatial distributions.
In order to facilitate an understanding of the effects of the initial velocity and spatial distributions on TOFMS 10 resolution, and of prior attempts at reducing these effects, reference is made to FIGS. 2-5. The structural features of the linear TOFMS 10 in FIGS. 2-5 are identical to that of FIG. 1 and the same reference characters are therefore used in the description of these FIGS.
In FIG. 2, an example is shown where two ions 30 and 32 have identical masses (as shown by the relative sizes of dots 30 and 32) and initial velocities (as shown by the magnitude of the arrows extending therefrom), but were displaced in space at ionization. Specifically, ion 30 began its acceleration toward the end 22 of the drift region 20 at a distance X.sub.0,1 from grid G.sub.0 12 and ion 32 began at a distance X.sub.0,2 from grid G.sub.0 12. This difference in starting positions affects the flight of the ions 30 and 32 in two ways. First, since ion 30 travels a shorter distance through the electric field E.sub.1, it receives less of a boost in kinetic energy (KE) due to electric field acceleration than does ion 32. In view of equation (1), ion 30 will therefore have less velocity than ion 32 upon arrival at grid G.sub.1 16. Second due to the starting positions X.sub.0,1 and X.sub.0,2, ion 32 has a greater total distance to travel than does ion 30. Both velocity and total distance traveled therefore influence the time of flight of each ion. Thus, although ions 30 and 32 have identical masses and ideally should therefore reach the end 22 of the drift region 20 simultaneously, a finite time differential may exist between their detection by detector 28 (not shown in FIG. 2), thereby increasing the measured time width (and decreasing resolution in the TOFMS 10) of this particular ion signal.
In FIG. 3, an example is shown where two ions 34 and 36 have identical masses and begin their acceleration toward the end 22 of the drift region 20 at the same distance X.sub.0 from grid G.sub.0 12, but have different initial velocities as shown by the magnitudes of the arrows extending therefrom. Since both ions 34 and 36 experience the same acceleration in electric fields E.sub.1 and E.sub.2, the total velocity of ion 36 will always be greater than that of ion 34 and it will therefore reach the end 22 of the drift region 20 before ion 34. As with the initial spatial differential example shown in FIG. 2, a difference in total velocity between ions 34 and 36, in this case due to different initial velocities, results in a variation in measured time of flight, and decreased TOFMS 10 resolution, of this particular ion signal.
In the TOFMS 10 of FIGS. 1-3, ions are formed from a gas phase sample circulating within region 1, typically by electron impact ionization or laser induced ionization. Ions so formed have a spatial distribution that is independent of their velocity distribution. In contrast, ions can also be produced in the source region (region 1) of TOFMS 10 from involatile molecules, i.e., those that remain on a surface until being desorbed into the gas phase by laser irradiation, particle bombardment or similar means. Desorption may produce neutral molecules (neutrals) for later ionization in the gas phase, and/or may produce gas phase ions directly from the sample surface. The instant of time t.sub.0 at which either desorbed neutrals are converted into ions in an electric field or, alternatively, the instant of time at which desorbed ions are accelerated toward a detector by a pulsed electric field (hereinafter referred to as an ion drawout electric field), provides the starting point for measuring ion flight times to the detector. In either case, the spatial and velocity distributions of ions at t.sub.0 are referred to as the initial spatial and velocity distributions. Following the drawout of ions by either technique, ion flight through a TOFMS, such as TOFMS 10, occurs in the same manner as described with respect to FIG. 1.
Referring now to FIG. 4, a sample 14 is deposited onto grid (or plate) G.sub.0 12 of TOFMS 10 for desorption of ions therefrom. With this approach, initial ion velocity distribution is a principal contributor to mass spectral peak broadening. When ions are desorbed/ionized from such a sample 14, their velocity distribution, as shown by arrows 38 and 40, is typically wider than those observed with gas phase samples. This is because of the energy required to induce the desportion, and results in further broadening of the mass spectral peaks and corresponding reduction in TOFMS 10 resolution.
Over the past several decades, many techniques have been developed to increase mass resolution in the TOFMS by compensating for the initial variations in ion velocity and position. Two noteworthy examples are the space focusing technique disclosed in U.S. Pat. No. 2,685,035 to Wiley and in Time-of-Flight Mass Spectrometer with Improved Resolution, Wiley, W. C. and McLaren, I. H., Rev. Sci. Instr. 26, 1150 (1955), and the development of a reflectron TOFMS as disclosed in The Mass-Reflectron, A New Nonmagnetic Time-of-Flight Mass Spectrometer With High Resolution, Mamyrin, B. A., Karataev, V. I., Shmikk, D. V. and Zagulin, V. A., Soy. Phys. JETP 37, 45 (1973).
Using the space focusing technique, an equation for total ion flight time is derived. The time of flight (TOF) is a function of the ion's mass to charge ratio (m/z), initial position (X.sub.0) and initial velocity (v.sub.0), the total distances of the various regions in the TOFMS (D.sub.x) and the strengths of the various electric fields established within the TOFMS (E.sub.x). In other words, EQU TOF=f(m/z, X.sub.0, v.sub.0, D.sub.x, E.sub.x) (2)
The partial derivative of equation (2) is taken with respect to X.sub.0, set equal to zero and solved for E.sub.x. This technique results in finding a set of grid voltages that establish the necessary electric fields for minimizing the effect of the initial variations in ion position. Although the corollary "velocity focusing" cannot be implemented (i.e., a set of practical electric fields that yield the result .differential.TOf/.differential.v.sub.0 =0 cannot be found), Wiley and McLaren further attempted to correct for the initial velocity distribution by providing a time delay between the formation and acceleration of the ions (called time lag focusing). They noted, however, that their initial spatial and velocity distributions are independent, and that time lag focusing necessarily violates space focusing conditions. Thus, depending on which distribution contributes more to mass spectral peak broadening, they concluded that time lag focusing may improve spectrometer resolution in some cases, but in other cases it will have a defocusing effect.
In the reflectron TOFMS, an ion mirror is placed in the flight path of the ion packets. If the mirror electrode voltages are arranged appropriately, the peak width contribution from the initial velocity distribution can be significantly reduced at the plane of the detector. In operation, the structural arrangement of the reflectron TOFMS requires ions produced with large velocities to travel greater distances than their slower counterparts, leading to narrowed temporal profiles at the detector. Such an instrument, however, is significantly more complicated than a linear TOFMS and still suffers from the initial ion spatial distribution discussed above.
In recent years, the formation of ions within a typical TOFMS has been routinely accomplished by direct desorption from a sample surface as previously discussed. Lasers ranging in wavelength from the far-UV to the far-IR have been used with a variety of organic and inorganic materials to generate ions for analysis by mass spectrometry, leading to the development and commercial availability of the laser microprobe mass analyzer (LAMMA) and the laser ionization mass analyzer (LIMA). Although widespread in use, these instruments were somewhat limited. Only atoms or molecules below a particular size could be desorbed either as intact ions or as intact neutrals that could be subsequently ionized in the gas phase. In the last few years, however, the ability to produce gas phase ions of large biomolecules and polymers was developed using a technique known as matrix-assisted laser desorption/ionization (MALDI). In addition to laser desorption, other ion formation techniques are known, such as fast atom bombardment (FAB), plasma desorption (PD) and the desorption of secondary ions from surfaces using primary ions in the keV energy region. The latter has led to the development of the secondary ion mass spectrometer (SIMS).
The recent popularity of MALDI has led to the modification of TOFMS 10 shown in FIG. 5. Since mass spectral peak broadening is believed to be dominated by the initial ion velocity distribution in desorption/ionization techniques, researchers have attempted to reduce its effect by using high ion drift energies. In what will hereinafter be referred to as the "traditional MALDI technique", ions generated within region 1 are accelerated to high velocities (to reduce the effect of initial ion velocity distribution on total velocity within the drift region) and then allowed to travel through the drift region 20 of increased length to a detector 110 located at the end 22 of the drift region 20. Thus, although "velocity focusing" per se cannot be performed, the effects of initial ion velocity distribution on mass spectral peak broadening can be reduced by using high drift velocities. This approach requires only a single acceleration region. A schematic of such an instrument 11 is shown in FIG. 5 wherein G.sub.2 18 of TOFMS 10 in FIG. 4 has been removed and the drift region 20' is extended to length L'.
Regardless of the ion formation method, each of the foregoing techniques and instruments is used with time-of-flight analysis in generating mass spectra. Thus, all suffer from the resolution limiting factors discussed above. Therefore, what is needed is a simple and effective technique for either eliminating or drastically reducing the effects of these distributions in a linear TOFMS in order to to increase mass spectral resolution in such an instrument.